Hematological MalignanciesPhase 2NCT02215070
Pasireotide in Prevention of GI Toxicity
A Phase 2 study testing Pasireotide in people with Hematological Malignancies, run by Anthony Sung, MD at 2 sites in United States.
Trial summary
The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic stem cell transplant. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hematological Malignancies
- What is being tested?
- Pasireotide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 2 sitesUnited States
- Study dates
- 21 Jan 2015to 15 Oct 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years of age or older at the time of study enrollment.
- Histologically confirmed diagnosis for which an allogeneic transplant is utilized.
- Plan to receive an allogeneic transplant from a 4-6/6 single or dual umbilical cord blood graft, or a 7-8/8 HLA-matched sibling or unrelated donor (High resolution HLA-A, B, C, DRB1).
- Meet standard criteria as defined by the institution for a myeloablative allogeneic stem cell transplantation, with myeloablative defined as using conditioning regimens containing:
- TBI ≥ 1200 cGy, or
- Busulfan ≥ 12.8mg/kg
- Patient must have given written informed consent according to FDA guidelines.
- Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
Who cannot join
- Female patients who are pregnant or lactating, or are of childbearing potential (FCBP, defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control
- FCBP must have a current negative serum pregnancy test prior to transplant per institutional practice.
- Use of an investigational drug within 1 month prior to dosing. Concurrent enrollment on other clinical research studies that contain an interventional therapy is not permitted while subjects are receiving pasireotide or within 5 half-lives of finishing pasireotide. However, subjects may concurrently enroll in non-interventional studies (e.g. biobanking, mobile health tracking).
- Active CNS disease (related to primary malignancy) at the time of enrollment.
- Patients with existing grade 2 toxicities, except as approved by the investigator.
- Any of the following diseases or conditions:
Show all 38Show fewer
- Cardiac:
- History of unexplained syncope or family history of idiopathic sudden death.
- Sustained or clinically significant cardiac arrhythmias.
- Risk factors for Torsades de Pointes such as:
- Uncontrolled hypokalemia
- Uncontrolled hypomagnesemia or hypermagnesemia
- Cardiac failure (New York Heart Association Class II or higher)
- Clinically significant/symptomatic bradycardia (HR < 50), or high-grade AV block.
- Known diagnosis of QT prolongation (QTc ≥ 470) or family history of long QT syndrome
- Concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure.
- Concomitant medications known to prolong the QT interval during the same time as pasireotide is to be administered (unless approved by PI and QTc < 470; standard transplant medications that are known to prolong the QT (e.g. azoles, ondansetron, etc.) are permitted but caution is advised and patients should be closely monitored).
- Endocrine:
- Uncontrolled diabetes at the time of cytoreduction. All patients with diabetes must be optimized on their diabetes regimen prior to initiating pasireotide.
- If a patient is diabetic: uncontrolled diabetes as defined by HbA1c > 8 per cent despite adequate therapy
- Patients who are not biochemically euthyroid. Patients with known history of hypothyroidism are eligible if they are on adequate and stable replacement thyroid hormone therapy for at least 3 months.
- Known diagnosis of hypocortisolism
- Known diagnosis of pituitary hormone deficiency.
- Known hypersensitivity to somatostatin analogs or any component of the pasireotide LAR or s.c. formulations.
- Infectious:
- Uncontrolled (not being treated) infections at the time of cytoreduction.
- A positive HIV test result (ELISA and Western blot) or history of known HIV. An HIV test will not be required; however, previous medical history will be reviewed.
- Gastrointestinal:
- Moderately impaired hepatic function (Child-Pugh B) or severe hepatic impairment (Child-Pugh C)
- Known gallbladder or bile duct disease, symptomatic cholelithiasis, acute or chronic pancreatitis.
- Known malabsorption syndrome, short bowel or chologenic diarrhea not controlled by specific therapeutic means.
- Hematologic:
- Abnormal coagulation (PT or aPTT > 30% above normal limits).
- Continuous anticoagulation therapy. Patients who were on anticoagulant therapy must complete a washout period of at least 10 days and have confirmed normal coagulation parameters before study inclusion.
- Miscellaneous:
- Major surgery/surgical therapy for any cause within 1 month prior to pasireotide administration. Patients should have recovered and have a good clinical condition before entering the study.
- Any co-morbid condition which, in the view of the Principal Investigator, renders the patient at high risk from treatment complications.
- Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Duke University Medical Center
Durham, North Carolina, 27705
About this study
Official title: Prevention of Gastrointestinal Toxicity From Total Body Irradiation or High Dose Chemotherapy With Pasireotide
The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic stem cell transplant. The study will also evaluate if Pasireotide is effective in reducing acute and chronic Graft-versus-Host-Disease (GvHD) after transplant.
Read the detailed description
The study design will be a non-randomized phase II. Forty patients receiving an ablative preparatory regimen will receive pasireotide subcutaneous (0.9 mg, b.i.d.) one day prior to initiation of the preparatory regimen and continuing for eight days following the completion of the preparatory regimen not to exceed 14 days total dosing. We select matched controls from existing patients who did not take the drug to minimize the time it takes to complete the trial.
Myeloablative preparatory regimens are defined as those including either TBI ≥ 1200 cGy or busulfan ≥ 12.8 mg/kg. The most common regimens combine TBI with cyclophosphamide (TBI/Cy) or busulfan with cyclophosphamide (Bu/Cy) (Appendix E). However, any regimen meeting the above definition of myeloablative preparatory regimen may be used.
The study will collect data at screening, at baseline prior to initiation of the drug (day of study drug start), transplant day 0, day +7, day +14 and weekly thereafter until day +100, and on days +180, +270, and +365. The total days on pasireotide therapy will be recorded as well as any SAE that is outside the expected for stem cell transplantation. We will also follow the incidence and severity of acute and chronic GVHD.
At Duke only, a video capsule endoscopy will be performed in a subset of ten study patients between transplant days +4 through +6. This substudy is descriptive in nature and only used to collect a source of preliminary data that may suggest further study.
Patients must agree to participate in this portion of the study and will be asked to sign a clinical consent for performance use of the video capsule endoscopy. Patients will be given detailed instructions to prepare for the procedure. An investigator who is blinded to the group allocation of the patients/volunteers separately will review the images obtained from each of the capsule examinations. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis. Each of these categories will be scored from 0-3 and summed to obtain an overall index that will range from 0 (normal study) to 12 (severely abnormal in all categories).
Citrulline assay Measurement of citrulline concentration has been used as a marker for cytotoxic treatment-induced intestinal damage and it is highly reproducible. The citrulline concentration appears to be a quantitative parameter that is independent of the underlying cause for epithelial cell loss and functions well in the post-SCT setting. Six mls of blood will be collected in heparinized tubes on days 0, 7, and 14. Tubes will be centrifuged according to manufacturer's instructions and the plasma will be collected and stored at -80C until shipment to the laboratory performing the assay.
Calprotectin assay Calprotectin has been described as another biomarker of GI injury. During radiation-induced inflammation, leucocytes infiltrate the mucosa and increase the level of fecal calprotectin. At least 50 mg of stool specimen will be collected from patients on days 0, 7, and 14. Samples will be stored at -80C until shipment to the laboratory performing the assay. Calprotectin will be measured with an ELISA kit (CALPRO, Oslo, Norway) in accordance with the manufacturer's instructions.
- Conditions
- Hematological Malignancies
- Being tested
- Pasireotide
- Keywords
- Allogeneic Stem Cell Transplantation, Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Acute Non-Lymphocytic Leukemia, Myelodysplastic Syndrome, Chronic Myeloid Leukemia, Lymphoma
- Medical subject headings
- Hematologic Neoplasms, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PasireotideDrug
Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant.
| Study group | Role | What they receive |
|---|---|---|
| Pasireotide + Preparatory Regimen | Experimental | Eligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant. Receives: Drug: Pasireotide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide
Number of participants who experience grades III-IV GI toxicity
Measured: 30 Days
Secondary outcomes (6)
Percentage of Acute GVHD
Number of participants who experience acute GVHD
Measured: 100 days
Maximum Severity of Acute GVHD Compared to Historical Controls
Assess maximum severity of acute GVHD scored as stage 1 (least severe) through stage 4 (most severe) using BMT CTN, 2013 standards
Measured: 100 days
Incidence of Chronic GVHD Compared to Historical Controls
Measure the number of participants who experience chronic GVHD
Measured: 1 year
Maximum Severity of Chronic GVHD Compared to Historical Controls
Assess maximum severity of chronic GVHD scored as none, mild, moderate or severe using 2014 NIH Consensus Criteria
Measured: 1 year
Overall Survival Compared to Historical Controls
Rate of overall survival of participants at one year post transplant
Measured: 1 year
Disease Free Survival Compared to Historical Controls
Rate of disease free survival of participants at one year post transplant
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2014 (estimated)
- Study start21 Jan 2015
- Primary completion28 Feb 2019
- Study completion15 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hematological MalignanciesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anthony Sung, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor-investigator, Anthony Sung, MD, Duke University
- Investigators
- Anthony Sung, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02215070
- Sponsor's protocol ID
- Pro00051736
- Status last verified
- Oct 2021
- First submitted
- 11 Aug 2014
- Last updated
- 17 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Gastrointestinal Toxicity From Total Body Irradiation or High Dose Chemotherapy With Pasireotide
- ClinicalTrials.gov ID
- NCT02215070
- Acronym / sponsor ID
- Pro00051736
- Conditions
- Hematological Malignancies
- Keywords
- Allogeneic Stem Cell Transplantation, Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Acute Non-Lymphocytic Leukemia, Myelodysplastic Syndrome, Chronic Myeloid Leukemia, Lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Anthony Sung, MDUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- 21 Jan 2015 (actual)
- Primary completion
- 28 Feb 2019 (actual)
- Study completion
- 15 Oct 2019 (actual)
- First posted
- 13 Aug 2014 (estimated)
- Results
- Posted 11 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate if the drug, Pasireotide, is safe and effective in reducing the gastrointestinal side effects of the drugs received to prepare for allogeneic stem cell transplant. The study will also evaluate if Pasireotide is effective in reducing acute and chronic Graft-versus-Host-Disease (GvHD) after transplant.
Detailed description
The study design will be a non-randomized phase II. Forty patients receiving an ablative preparatory regimen will receive pasireotide subcutaneous (0.9 mg, b.i.d.) one day prior to initiation of the preparatory regimen and continuing for eight days following the completion of the preparatory regimen not to exceed 14 days total dosing. We select matched controls from existing patients who did not take the drug to minimize the time it takes to complete the trial.
Myeloablative preparatory regimens are defined as those including either TBI ≥ 1200 cGy or busulfan ≥ 12.8 mg/kg. The most common regimens combine TBI with cyclophosphamide (TBI/Cy) or busulfan with cyclophosphamide (Bu/Cy) (Appendix E). However, any regimen meeting the above definition of myeloablative preparatory regimen may be used.
The study will collect data at screening, at baseline prior to initiation of the drug (day of study drug start), transplant day 0, day +7, day +14 and weekly thereafter until day +100, and on days +180, +270, and +365. The total days on pasireotide therapy will be recorded as well as any SAE that is outside the expected for stem cell transplantation. We will also follow the incidence and severity of acute and chronic GVHD.
At Duke only, a video capsule endoscopy will be performed in a subset of ten study patients between transplant days +4 through +6. This substudy is descriptive in nature and only used to collect a source of preliminary data that may suggest further study.
Patients must agree to participate in this portion of the study and will be asked to sign a clinical consent for performance use of the video capsule endoscopy. Patients will be given detailed instructions to prepare for the procedure. An investigator who is blinded to the group allocation of the patients/volunteers separately will review the images obtained from each of the capsule examinations. Images will be examined for evidence of the four following types of abnormalities: reddened/edema/villous blunting, erosion, ulcer and stenosis. Each of these categories will be scored from 0-3 and summed to obtain an overall index that will range from 0 (normal study) to 12 (severely abnormal in all categories).
Citrulline assay Measurement of citrulline concentration has been used as a marker for cytotoxic treatment-induced intestinal damage and it is highly reproducible. The citrulline concentration appears to be a quantitative parameter that is independent of the underlying cause for epithelial cell loss and functions well in the post-SCT setting. Six mls of blood will be collected in heparinized tubes on days 0, 7, and 14. Tubes will be centrifuged according to manufacturer's instructions and the plasma will be collected and stored at -80C until shipment to the laboratory performing the assay.
Calprotectin assay Calprotectin has been described as another biomarker of GI injury. During radiation-induced inflammation, leucocytes infiltrate the mucosa and increase the level of fecal calprotectin. At least 50 mg of stool specimen will be collected from patients on days 0, 7, and 14. Samples will be stored at -80C until shipment to the laboratory performing the assay. Calprotectin will be measured with an ELISA kit (CALPRO, Oslo, Norway) in accordance with the manufacturer's instructions.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pasireotide + Preparatory Regimen | Experimental | Drug: PasireotideEligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years of age or older at the time of study enrollment.
- Histologically confirmed diagnosis for which an allogeneic transplant is utilized.
- Plan to receive an allogeneic transplant from a 4-6/6 single or dual umbilical cord blood graft, or a 7-8/8 HLA-matched sibling or unrelated donor (High resolution HLA-A, B, C, DRB1).
- Meet standard criteria as defined by the institution for a myeloablative allogeneic stem cell transplantation, with myeloablative defined as using conditioning regimens containing:
- Patient must have given written informed consent according to FDA guidelines.
Key exclusion criteria (38 listed)
- Female patients who are pregnant or lactating, or are of childbearing potential (FCBP, defined as all women physiologically capable of becoming pregnant) and not practicing an effective method of contraception/birth control
- FCBP must have a current negative serum pregnancy test prior to transplant per institutional practice.
- Use of an investigational drug within 1 month prior to dosing. Concurrent enrollment on other clinical research studies that contain an interventional therapy is not permitted while subjects are receiving pasireotide or within 5 half-lives of finishing pasireotide. However, subjects may concurrently enroll in non-interventional studies (e.g. biobanking, mobile health tracking).
- Active CNS disease (related to primary malignancy) at the time of enrollment.
- Patients with existing grade 2 toxicities, except as approved by the investigator.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PasireotideEligible subjects will receive pasireotide daily for 5 days before stem cell transplant, the day of the stem cell transplant, and daily for 8 days following the stem cell transplant. Preparatory regimen will be given 4 days before stem cell transplant. | Drug | Pasireotide + Preparatory Regimen |
Primary outcome
Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide
Time frame: 30 Days
Number of participants who experience grades III-IV GI toxicity
6 secondary outcomes
Percentage of Acute GVHD
Time frame: 100 days
Maximum Severity of Acute GVHD Compared to Historical Controls
Time frame: 100 days
Incidence of Chronic GVHD Compared to Historical Controls
Time frame: 1 year
Maximum Severity of Chronic GVHD Compared to Historical Controls
Time frame: 1 year
Overall Survival Compared to Historical Controls
Time frame: 1 year
Disease Free Survival Compared to Historical Controls
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Sung, MD principal investigator
Duke University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pasireotide in people with Hematological Malignancies, run by Anthony Sung, MD at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of GI Toxicity From the Preparatory Regimen and the GVHD Prophylaxis in Stem Cell Transplantation (SCT) Patients Who Are Treated With Pasireotide (time frame: 30 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Nov 2021.